A mutation in a thioredoxin reductase homolog suppresses p53-induced growth inhibition in the fission yeastSchizosaccharomyces pombe

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Abstract
A strong growth inhibition is observed when the human p53 tumor suppressor gene product is expressed in the fission yeastSchizosaccharomyces pombe. This growth inhibition is specific for wild-type p53; mutant alleles of p53 derived from human tumors show a greatly decreased ability to inhibit growth. These data suggest that there may be a p53-responsive pathway inS. pombe. To identify elements in this pathway genetically, we isolated a mutant yeast strain in which the growth inhibitory activity of p53 is largely suppressed. In addition, the activity of p53 as a transcription factor is also decreased in this strain. The suppression of p53 activity is not due to a decrease in p53 expression or a failure of p53 to localize to the nucleus. This p53 suppressor mutation is in a novelS. pombe gene with homology to thioredoxin reductase genes, and has been namedtrr1. Strains with a mutation of, or deletion in,trr1 are sensitive to oxidizing agents, suggesting that thetrr1 suppressor mutation causes partial loss oftrr1 function. Since oxidizing agents are able to suppress p53 activity in vitro, thistrr1 mutation may affect the activity of p53 in fission yeast by increasing the oxidation state of the tumor suppressor.